ArticleThe Journal of biological chemistry2012
Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 86 citations in OpenAlex.
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- Rapid Divergence of Visual Systems and Signaling Traits to Contrasting Light Regimes During Early Speciation of African Crater Lake Cichlid Fish.Molecular biology and evolution · 2025Article
- Advances and therapeutic opportunities in visual cycle modulation.Progress in retinal and eye research · 2025Review
- Genetic context modulates aging and degeneration in the murine retina.Molecular neurodegeneration · 2025Article
- Activation of GSDME by all-International journal of biological sciences · 2025Article
- Retinal Degeneration Associated With Biallelic RDH12 Variants: Longitudinal Evaluation of Retinal Structure and Visual Function in Pediatric Patients.Investigative ophthalmology & visual science · 2024Article
- Sphingolipid Levels and Processing of the Retinyl Chromophore in the Retina of a Mouse Model of Niemann-Pick Disease.Investigative ophthalmology & visual science · 2024Article
- Glutamine is the only amino acid that can adequately support the generation of NADPH in rod photoreceptors.Experimental eye research · 2024Article
- RDH12 allows cone photoreceptors to regenerate opsin visual pigments from a chromophore precursor to escape competition with rods.Current biology : CB · 2024Article
- Report From the Second Global Scientific Conference on Clinical Trial Design and Outcome Measures for RDH12-Associated Inherited Retinal Degeneration.Translational vision science & technology · 2024Article
- The First Steps of the Visual Cycle in Human Rod and Cone Photoreceptors.Investigative ophthalmology & visual science · 2024Article
- Genetic context modulates aging and degeneration in the murine retina.bioRxiv : the preprint server for biology · 2024Article
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- High temperature influences DNA methylation and transcriptional profiles in sea urchins (Strongylocentrotus intermedius).BMC genomics · 2023Article
- A Splicing Variant in RDH8 Is Associated with Autosomal Recessive Stargardt Macular Dystrophy.Genes · 2023Article
- Primary versus Secondary Elevations in Fundus Autofluorescence.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
In vertebrate rod cells, retinoid dehydrogenases/reductases (RDHs) are critical for reducing the reactive aldehyde all-trans-retinal that is released by photoactivated rhodopsin, to all-trans-retinol (vitamin A). Previous studies have shown that RDH8 localizes to photoreceptor outer segments and is a strong candidate for performing this role. However, RDH12 function in the photoreceptor inner segments is also key, because loss of function mutations cause retinal degeneration in some forms of Leber congenital amaurosis. To investigate the in vivo roles of RDH8 and RDH12, we used fluorescence imaging to examine all-trans-retinol production in single isolated rod cells from wild-type mice and knock-out mice lacking either one or both RDHs. Outer segments of rods deficient in Rdh8 failed to reduce all-trans-retinal, but those deficient in Rdh12 were unaffected. Following exposure to light, a leak of retinoids from outer to inner segments was detected in rods from both wild-type and knock-out mice. In cells lacking Rdh8 or Rdh12, this leak was mainly all-trans-retinal. Wild-type rods incubated with all-trans-retinal reduced moderate loads of retinal within the cell interior, but this ability was lost by cells deficient in Rdh8 or Rdh12. Our findings are consistent with localization of RDH8 to the outer segment where it provides most of the activity needed to reduce all-trans-retinal generated by the light response. In contrast, RDH12 in inner segments can protect vital cell organelles against aldehyde toxicity caused by an intracellular leak of all-trans-retinal, as well as other aldehydes originating both inside and outside the cell.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.